High-throughput Screening in Larval Zebrafish Identifies Novel Potent Sedative-hypnotics

Yang, Xiaoxuan; Jounaïdi, Youssef; Dai, Jiazhong; Marte-Oquendo, Francisco; Halpin, Elizabeth S.; Brown, Lauren E.; Trilles, Richard; Xu, Wenqing; Daigle, Renee V.; Yu, Bo; Schaus, Scott E.; Porco, John A.; Forman, Stuart A.

doi:10.1097/aln.0000000000002281

Cited by 33 publications

(28 citation statements)

References 57 publications

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“…Interestingly, in previous studies dexmedetomidine did show complete loss of movement while using the light reflex 23 . When comparing the values obtained from Yang et al 23 using 7 dpf zebrafish larvae, the spontaneous movement numbers were very similar and the response to the light stimulus gave an EC50 between that of SPONT and ELEC (Table 1). This would suggest that the light stimulus may model a lighter sedation than the ELEC or TAP but more than the SPONT.…”

Section: Discussionmentioning

confidence: 82%

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A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states

Bedell

Meng

Pack

et al. 2020

Sci Rep

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The field of neuropharmacology has not yet achieved a full understanding of how the brain transitions between states of consciousness and drug-induced unconsciousness, or anesthesia. Many small molecules are used to alter human consciousness, but the repertoire of underlying molecular targets, and thereby the genes, are incompletely understood. Here we describe a robust larval zebrafish model of anesthetic action, from sedation to general anesthesia. We use loss of movement under three different conditions, spontaneous movement, electrical stimulation or a tap, as a surrogate for sedation and general anesthesia, respectively. Using these behavioral patterns, we find that larval zebrafish respond to inhalational and IV anesthetics at concentrations similar to mammals. Additionally, known sedative drugs cause loss of spontaneous larval movement but not to the tap response. This robust, highly tractable vertebrate model can be used in the detection of genes and neural substrates involved in the transition from consciousness to unconsciousness.

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Section: Discussionmentioning

confidence: 82%

“…The pKa for each drug is shown, demonstrating that only the ketamine had a pKa higher than the pH 7.2 of the E3. Data from Yang et al 23 in 7 dpf zebrafish larvae demonstrates similar concnetrations for SPONT with lower concentrations for the stimulus. Both our data and the 7 dpf data are within clinical range when compared to human data.…”

mentioning

confidence: 68%

A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states

Bedell

Meng

Pack

et al. 2020

Sci Rep

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“…Anesthetic administration is more straightforward, as any drug that can be solubilized in pond water will be rapidly absorbed via diffusion through the skin or across the gills, and can be used for high-throughput screening. 65 There may be little advantage for the study of aging, or age-related processes like neurodegeneration, since their life span is similar to the mouse, so the examination of aged fish becomes difficult. Nevertheless, models of Alzheimer disease-like neurodegeneration have been reported for both adult and larval zebrafish.…”

Section: Danio Rerio (Zebrafish)mentioning

confidence: 99%

Perioperative Neurocognitive Disorder

et al. 2020

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The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors’ goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and “best practices” in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

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“…Larval zebrafish are amenable to high-throughput screen due to their transparency, small size and high permeability to small molecules (Kokel et al, 2010; Rihel et al, 2010). Though most high-throughput systems are designed for drug or genetic screens (Gehrig et al, 2018; Rihel et al, 2010; Yang et al, 2018), here we have developed a high-throughput behavioral training system with custom supported software suites. Compared with previous work (Hinz et al, 2013; Pelkowski et al, 2011), the BLITZ software has enabled a fully automatic control of video capture, online image processing, visual pattern presentation and electroshocks delivery, making it an easily adaptable system for various purposes.…”

Section: Discussionmentioning

confidence: 99%

Visual intensity ratio modulates operant learning responses in larval zebrafish

Yang

Meng

et al. 2018

Preprint

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13Larval zebrafish is a promising vertebrate model for understanding neural 14 mechanisms underlying learning and memory. Here, we report on a high-throughput 15 operant learning system for zebrafish larvae and demonstrate that lower visual 16 intensity ratio of the conditioned stimulus to the background can enhance learning 17 ability, highlighted by several behavioral metrics. We further characterize the learning 18 curves as well as memory extinction for each conditioned pattern. Finally, we show 19 how this learning process developed from 7 days old to 10 days old zebrafish. 20 Highlights 21  Conditioned visual patterns with lower intensity ratio to the background elicited 22 stronger operant learning responses 23  Memory extinction was modulated by the visual intensity ratio of the conditioned 24 stimulus to the background 25  A high-throughput automated system for acquiring and analyzing behavioral data 26 27 2 Material and Methods 61 2.1 Ethical statement of animals-using 62 Handling and care of all animals were conducted in strict accordance with the 63 guidelines and regulations set forth by University of Science and Technology of 64 China (USTC) Animal Resources Center, and University Animal Care and Use 65 Committee. Both raising and training protocols were approved by the Committee on 66 the Ethics of Animal Experiments of the USTC (permit number: 67 USTCACUC1103013). 68 2.2 Animals and raising 69 Zebrafish (Danio rerio) of the genotype huc:h2b-gcamp6f were used in all 70 experiments. All tested fish were from 7 to 10 dpf (day past fertilization) larvae. They 71 were bred, raised and housed in the same environment. Fish were fed two times per 72 day from 6 dpf with paramecium in the morning (8-9 A.M.) and evening (6-7 P.M.) 73 until used in the experiments. Water was replaced with E2 medium (Cunliffe, 2003) 74 in the morning (8-9 A.M.) and evening (6-7 P.M.). Water temperature was maintained 75 at 28.5 °C. Illumination was provided by fluorescent light tubes from the ceiling with 76 lights turned on at 08:00 A.M. and off at 10:00 P.M. 77 2.3 Experimental Setup 78 The behavioral system with custom software suites and supported hardware were built 79 to achieve an end-to-end high-throughput experimental workflow. (Figure 1A) 80 2.3.1 Hardware 81Zebrafish swam freely in custom-built acrylic containers with transparent bottoms. 82Each container was divided into four arenas separated by opaque walls. The arena's 83 size is 3 cm × 3 cm × 1 cm, with water filled (Fig. S2.a). Each arena held one fish. 84 Three CMOS cameras (Basler aca2000-165umNIR, Germany) with adjustable lens 85 (Canon, Model EF-S 18-55mm f/3.5-5.6 IS II, Japan) simultaneously captured 86 swimming behavior at ten frames per second. Three infrared LED light sources 87 (Kemai Vision, China, model HF-FX90, wavelength 940 nm) illuminated each 88 container from below. A 700 nm long-pass filter (Thorlabs FEL0700, US.) was 89 positioned in front of each camera to block visible light to facilitate online imaging 90 processing with custom soft...

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High-throughput Screening in Larval Zebrafish Identifies Novel Potent Sedative-hypnotics

Cited by 33 publications

References 57 publications

A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states

A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states

Perioperative Neurocognitive Disorder

Visual intensity ratio modulates operant learning responses in larval zebrafish

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